Manufacture of 5-nitro-2-aminoanisole



Patented June 19, 1934 UNITED STATES 7 1,963,598 MANUFACTURE OFs-m'rno-z-nmmo- ANISOL Jo n M. Tinker and Louis Spiegler, SouthMilwaukee, Wis'., assignors to E. I. du Pont de Nemours & Company,Wilmington, DeL, a corporation of Delaware No Drawing. ApplicationJanuary 25, 1932,

Serial No. 588,816

Claims. (Cl. 260-124) This invention relates to the manufacture of5-nitro-2-anisidine. It is an object of this invention to provide aprocess for the manufacture of 5-nitro-2-anisidine whereby the same isobtained 5; in good yield and in great predominance over the d-nitroisomer. A further object of this invention is to provide a simple andeflicient process for the manufacture of 5-nitro-2-anisidine by usingthe requisite initial materials in economical 101 quantities. Other andfurther important objects of this invention will appear as thedescription proceeds.

By 5-nitro-2-anisidine and 4-nitro-2-anisidine, we are referringrespectively to the follow- 151 ing two compounds:

o on; 0 on,

2 5-11itro-2-anisidine 4-nitro-2'anisidine the orientation of thesubstituents being taken with respect to the OCI-Ia group. Thesecompounds may also be designated respectively as5-nitro-2-amino-1-anisole and 4-nitro-2-amino- 301 l-anisole.

5-nitro-2-amino-1-anisole has been prepared in the art by reacting uponacetaniside (2-'-acetylamino-l-anisole) with an excess of'nitric acid,either in the presence or absence of acetic acid. (German Patent No.98,637; Friedlander, V, 67). This process produces a mixture of the5-nitro and -4'-nitro isomers, the ratio of the two depend ing on theparticular conditions of nitration. A more serious objection, however,is the'fact that 4 this process requires prohibitive and wastefulexcesses of nitric acid, thus rendering the process impractical forcommercial purposes. To remedy this objection an attempt was'made intheart to use concentrated sulfuric acid as solvent for the nitrationmass. It was found, however, that this process leads almost exclusivelyto the formation of the 4-nitro isomer. (Georges Freyss, Bull. Soc.Ind., Mulhouse, 70, 375-383; Chemisches Centralblatt, 1901, I, 739.)

We have now made the surprising discovery that if instead ofconcentrated sulfuric acid, dilute sulfuricacid is used, the reactionproceeds smoothly toward the production of a mixture of nitro-anisidinesin which the 5-nitro isomer pre- 551 dominates. More particularly, wefound that if crystallize out.

acetyl-o-anisidine is treated with 1 to 3 mole of nitric acid in amedium of sulfuric acid of less strength than B., a product resultscontaining a mixture of 5-nitro-2-anisidine and 4-nitro- 2-anisidine ina ratio varying with the specific 00 conditions of nitration, but beinggenerally in the neighborhood of 2:1.

Based on this discovery, our novel process conists of treatingacetyl-o-anisidine with nitric acid in'a medium of sulfuric acid of lessstrength than 60 B. but of sufficient concentration to keep the entiremass in solution during the nitration. In its more preferred form, ourprocess consists of reacting upon acetyl-o-anisidine with about 1 to 3molal ratios of nitric acid in the presence of aqueous sulfuric acid of55 to 78% strength. The reaction mass is then drowned in water toprecipitate a mixture of 5-nitro-2-acetylamino-anisole and related nitrobodies. The precipitate is then filtered off, treated with causticalkali to hydrolyze the acetylamino group, the resulting mixture ofnitro-anisidines is again filtered off and heated in sulfuric acid ofabout 3 to 8% strength to convert the mixture of amines into thecorresponding sulfates. Upon vcooling 3,9 and diluting the sulfate of5-nitro-2-anisidine precipitates, while the sulfates of the 4-isomer andother nitration products stay in solution; Filtration of the latter massfinally gives 5-nitroz-anisidine sulfate substantially free from iso- 3imers.

Other concentrations of sulfuric acid may be used in the nitration step,but are not advantageous. The use of sulfuric acid of a strength below55% decreases the speed of nitration, unless excessive quantities ofeither nitric or sulfuric acid be used. Also, the reaction mass undersuch low concentration of H2804 tends to Theme of concentrated sulfuricacid above 78% (60 B.) decreases the ratio of 9 5 the 5-nitro isomer inthe product, 7

For best results, the concentration of sulfuric acid should be graduallybuilt up, as the reaction proceeds, from a value near the lowerconcentration limit above stated to one near the higher limit. Theobject of this is to bring back into solution any of the acetylamino'anisole which mayhave precipitated out during the reaction, while atthe same time avoiding excesses of sulfuric acid beyond the minimumconcentration required for complete solution of the reaction mass,especially during the initial *stagesof the reaction.

The quantity of nitric acid used may vary from about one to three molesfor each mole of acetyl- 1 o-anisidine. The yield generally increaseswith the larger quantities of nitric acid.

For best results, the temperature of the reaction mass should be keptbetween 18 and 25 C., although some variation outside these limits ispermissible. Below 0., however, the reaction proceeds at a very slowrate, and contains further the danger of starting suddenly at anuncontrollable rate. Again, above 38 C., the nitration proceeds too fastfor proper control, and results in a decreased yield of the desiredproduct.

Without limiting our invention to any particular procedure, thefollowing example is given to illustrate our preferred mode ofoperation. Parts given are parts by weight.

Example 565 parts of 63% nitric acid, 790 parts of 60 Be. sulfuric acidand 60 parts of water are charged into an enameled vessel. 440 parts ofN-acetyl-o-anisidine (prepared from 320 parts of o-anisidine) and 1950parts of 60 Be. sulfuric acid are added alternately in small portions,while maintaining the temperature at 25 C. The addition of said twocompounds is preferably carried out in the following manner: At firstthe acetyl body is added in small quantities untilnitro-2-acetylamino-anisole starts to crystallize out. Sulfuric acid isthen added until the mass is reconverted intoa clear solution. Theprocedure is then repeated until the entire quantities ofacetyl-o-anisidine and sulfuric acid above specified have beenintroduced. The mass is now stirred for 1 hour at about C., poured intoa mixture of water and ice, and filtered. The filter cake is washedacid-free and then suspended in 855 parts of denatured alcohol andheated to 70 C. 112 parts of caustic soda, dissolved in water to a 70%solution, are added gradually over a period of three hours, whilemaintaining the mass at 70-75 C., to hydrolyze off the acetyl group. Themass is now diluted with water to a total of about 2500 parts, cooled to15 C., and filtered. The filter cake consists of a mixture ofnitro-o-anisidines, and melts at 114-119 C. Analysis shows it to consistsubstantially of 5- and l-nitro-o-anisidines in the ratio of about 2:1,respectively. From this mixture the bulk of 5-nitro-2- amino-anisole maybe recovered substantially free of isomers by dissolving the entire massin 3200 parts of hot, 5% sulfuric acid, and then cooling to about 15 0.,whereby the sulfate of 5-nitro-2-anisidine precipitates. The mass isthen filtered and washed with dilute sulfuric acid. On basing withcaustic soda and drying, it melts at 140-1415" C.

From the mother liquors the i-nitro-isomer may be recovered in anysuitable manner.

If desired the first filtration step, namely the filtration of themixture of nitro-acetylaminoanisoles may be dispensed with. Instead, thedrowned reaction mass may be boiled directly to split off the acetylgroup, and then cooled to precipitate 5-nitro-2-amino-anisole in theform of its sulfate, which may be then filtered off and washed as above.

Many variations and modifications are possible in our preferredprocedure, without departing from the spirit of this invention, as willbe readily understood to those skilled in the art.

We claim:

1. A process for preparing 5-nitro-2-aminoanisole which comprises thestep of reacting upon N-acetyl-o-anisidine with nitric acid in a mediumof sulfuric acid of less strength than 60 B.

2. A process for preparing 5-nitro-2-aminoanisole which comprises thestep of reacting upon N-acetyl-o-anisidine with nitric acid in a mediumof sulfuric acid of 55 to 78% strength.

3. A process for preparing 5-nitro-2-acety1- amino-anisole whichcomprises reacting upon N-acetyl-o-anisidine with 1 to 3 molal ratios ofnitric acid in a medium of aqueous sulfuric acid of 55 to 78% strengthand at a temperature between 15 and C.

4. A process for preparing 5-nitro-2-acetylamino-anisole which comprisesreacting upon N-acetyl-o-anisidine with 1 to 3 molal ratios of nitricacid in a medium of aqueous sulfuric acid of to 78% strength, at atemperature between 18 and 25 0., diluting the reaction mass, andrecovering a mixture of nitro-acetylamino-anisoles.

5. A process for preparing 5-nitro-2-acetylamino-aniso1e which comprisesreacting upon N-acetyl-o-anisidine with 1 to 3 molal ratios of nitricacid in a medium of aqueous sulfuric acid increasing in concentration,as the reaction proceeds, from about 55 to about 78% strength, dilutingthe reaction mass, and recovering the precipitatednitro-acetylaminoanisole.

6. A process for preparing S-nitro-Z-aminoanisole which comprisesreacting upon N-acetylo-anisidine with 1 to 3 molal ratios of nitricacid in a medium of aqueous sulfuric acid of 55 to 78 strength, dilutingthe reaction mass, hydrolyzing oif the acetyl group, and recovering5-nitro- Z-amino-anisole in the form of its sulfate.

7. A process for preparing 5-nitro-2-aminoanisole which comprisesreacting upon N-acetylo-anisidine with 1 to 3 molal ratios of nitricacid, at a temperature between 18 and 25 C. and in a medium of aqueoussulfuric acid of 55 to 78% strength, diluting the reaction mass,recovering the precipitated mass of nitroacetylaminoanisole, hydrolyzingoff the acetyl group, and recovering 5-nitro-2-amino-anisole in the formof its sulfate.

8. A process for preparing 5-nitro-2-aminoanisole which comprisesreacting upon N-acetylo-anisidine with 1 to 3 molal ratios of nitricacid in a medium of aqueous sulfuric acid of 55 to 78% strength,diluting the reaction mass, recovering the precipitated mass ofnitro-acetylaminoanisole, hydrolyzing off the acetyl group, recovering5-nitro-2-amino-anisole in the form of its sulfate, and treating thelatter with aqueous alkali to form the free base.

9. In the process of preparing 5-nitro-2-aminoanisole by reacting upono-acetylamino-anisole with aqueous nitric acid, the step of effectingthe reaction in an aqueous sulfuric acid medium of a strength notsubstantially higher than the minimum required for keeping the entirereaction mass in solution under the particular working conditions.

10. In the process of preparing 5-"1itro-2- anisidine by nitratingN-acetyl-o-anisidine, the improvement which comprises effecting thenitration in a sulfuric acid medium of 55 to 78% strength and at atemperature between 15 and 30 C.

JOHN M. TINKER. LOUIS SPIEGLER.

